Fig. 7: Working model for Sac1 controlled TGN V-ATPase activity and downstream effects.
From: Control of Golgi- V-ATPase through Sac1-dependent co-regulation of PI(4)P and cholesterol
Sac1 fuelled PI(4)P/cholesterol exchange maintains the composition of the Golgi membrane, allowing V-ATPase assembly for TGN acidification, proper terminal glycosylation and cargo secretion. Rapidly after Sac1 degradation, PI(4)P is accumulated in the TGN while cholesterol is depleted. This changes the lipid microenvironment of the V0 region, resulting in a conformational change in the V0a2 subunit which prevents the assembly of the Golgi V-ATPase complex. This results in the deacidification of the TGN, Golgi fragmentation and defects in cargo processing and secretion.
